A physiologic neonatal animal preparation has been developed for chronic cardiovascular studies of pulmonary and systemic vascular resistance and investigation of the role of the histamine H1 and H2 receptors in normal pulmonary vascular tone and in pulmonary vasculature constricted by hypoxis. Tolazoline is administered frequently to infants with fulmonary artery hypertension and often improves pulmonary perfusion; its actions involve histamine H1 and H2 receptors. Chemical analyses of the H1 antagonist chlorpheniramine, the H2 antagonist cimetidine and the histamine agonist tolazoline will be utilized to design drug dosages that achieve steady state agonist/antagonist plasma concentrations and thus constant receptor concentrations. Steady state plasma antagonist concentrations will be established to determine whether quantitative antagonism of the H1 and H2 receptors can alter normal pulmonary vascular tone, pulmonary vascular tone constricted by hypoxia, or the cardiovascular actions of tolazoline. Cardiovascular H1 and H2 receptor affinity constants will be calculated for tolazoline and other histamine receptor agonists with Schild plots. Tolazoline pharmacokinetics and plasm concentrations in newborn infants will be correlated with cardiovascular responses. Pharmacologic manipulation of histamine H1 and histamine H2 receptors may providenew therapeutic approaches to management of pulmonary hypertension.